To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Healthcare personnel with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection were interviewed to describe activities and practices in and outside the workplace. Among 2,625 healthcare personnel, workplace-related factors that may increase infection risk were more common among nursing-home personnel than hospital personnel, whereas selected factors outside the workplace were more common among hospital personnel.
The invention of silicon drift detectors has resulted in an unprecedented improvement in detection efficiency for energy-dispersive X-ray (EDX) spectroscopy in the scanning transmission electron microscope. The result is numerous beautiful atomic-scale maps, which provide insights into the internal structure of a variety of materials. However, the task still remains to understand exactly where the X-ray signal comes from and how accurately it can be quantified. Unfortunately, when crystals are aligned with a low-order zone axis parallel to the incident beam direction, as is necessary for atomic-resolution imaging, the electron beam channels. When the beam becomes localized in this way, the relationship between the concentration of a particular element and its spectroscopic X-ray signal is generally nonlinear. Here, we discuss the combined effect of both spatial integration and sample tilt for ameliorating the effects of channeling and improving the accuracy of EDX quantification. Both simulations and experimental results will be presented for a perovskite-based oxide interface. We examine how the scattering and spreading of the electron beam can lead to erroneous interpretation of interface compositions, and what approaches can be made to improve our understanding of the underlying atomic structure.
When presenting with a first episode of psychosis (FEP), migrants can have different demographic and clinical characteristics to the native-born population and this was examined in an Irish Early Intervention for Psychosis service.
All cases of treated FEP from three local mental health services within a defined catchment area were included. Psychotic disorder diagnoses were determined using the SCID and symptom and functioning domains were measured using validated and reliable measures.
From a cohort of 612 people, 21.1% were first-generation migrants and there was no difference in the demographic characteristics, diagnoses, symptoms or functioning between migrants and those born in the Republic of Ireland, except that migrants from Africa presented with less insight. Of those admitted, 48.6% of admissions for migrants were involuntary compared to 37.7% for the native-born population (p = 0.09).
First-generation migrants now make up a significant proportion of people presenting with a FEP to an Irish EI for psychosis service. Broadly the demographic and clinical characteristics of migrants and those born in the Republic of Ireland are similar, except for less insight in migrants from Africa and a trend for a higher proportion of involuntary admissions in the total migrant group.
We aimed to investigate the associations of poor oral health cross-sectionally with diet quality and intake in older people. We also examined whether change in diet quality is associated with oral health problems. Data from the British Regional Heart Study (BRHS) comprising British males aged 71–92 years and the Health, Aging and Body Composition (HABC) Study comprising American males and females aged 71–80 years were used. Dental data included tooth loss, periodontal disease, dry mouth and self-rated oral health. Dietary data included diet quality (based on Elderly Dietary Index (BRHS) and Healthy Eating Score (HABC Study)) and several nutrients. In the BRHS, change in diet quality over 10 years (1998–2000 to 2010–2012) was also assessed. In the BRHS, tooth loss, fair/poor self-rated oral health and accumulation of oral health problems were associated with poor diet quality, after adjustment. Similar associations were reported for high intake of processed meat. Poor oral health was associated with the top quartile of percentage of energy content from saturated fat (self-rated oral health, OR 1·34, 95 % CI 1·02, 1·77). In the HABC Study, no significant associations were observed for diet quality after adjustment. Periodontal disease was associated with the top quartile of percentage of energy content from saturated fat (OR 1·48, 95 % CI 1·09, 2·01). In the BRHS, persistent low diet quality was associated with higher risk of tooth loss and accumulation of oral health problems. Older individuals with oral health problems had poorer diets and consumed fewer nutrient-rich foods. Persistent poor diet quality was associated with oral health problems later in life.
Efforts to move community engagement in research from marginalized to mainstream include the NIH requiring community engagement programs in all Clinical and Translational Science Awards (CTSAs). However, the COVID-19 pandemic has exposed how little these efforts have changed the dominant culture of clinical research. When faced with the urgent need to generate knowledge about prevention and treatment of the novel coronavirus, researchers largely neglected to involve community stakeholders early in the research process. This failure cannot be divorced from the broader context of systemic racism in the US that has contributed to Black, Indigenous, and People of Color (BIPOC) communities bearing a disproportionate toll from COVID-19, being underrepresented in COVID-19 clinical trials, and expressing greater hesitancy about COVID-19 vaccination. We call on research funders and research institutions to take decisive action to make community engagement obligatory, not optional, in all clinical and translational research and to center BIPOC communities in this process. Recommended actions include funding agencies requiring all research proposals involving human participants to include a community engagement plan, providing adequate funding to support ongoing community engagement, including community stakeholders in agency governance and proposal reviews, promoting racial and ethnic diversity in the research workforce, and making a course in community engaged research a requirement for Masters of Clinical Research curricula.
Typical enteropathogenic Escherichia coli (tEPEC) infection is a major cause of diarrhoea and contributor to mortality in children <5 years old in developing countries. Data were analysed from the Global Enteric Multicenter Study examining children <5 years old seeking care for moderate-to-severe diarrhoea (MSD) in Kenya. Stool specimens were tested for enteric pathogens, including by multiplex polymerase chain reaction for gene targets of tEPEC. Demographic, clinical and anthropometric data were collected at enrolment and ~60-days later; multivariable logistic regressions were constructed. Of 1778 MSD cases enrolled from 2008 to 2012, 135 (7.6%) children tested positive for tEPEC. In a case-to-case comparison among MSD cases, tEPEC was independently associated with presentation at enrolment with a loss of skin turgor (adjusted odds ratio (aOR) 2.08, 95% confidence interval (CI) 1.37–3.17), and convulsions (aOR 2.83, 95% CI 1.12–7.14). At follow-up, infants with tEPEC compared to those without were associated with being underweight (OR 2.2, 95% CI 1.3–3.6) and wasted (OR 2.5, 95% CI 1.3–4.6). Among MSD cases, tEPEC was associated with mortality (aOR 2.85, 95% CI 1.47–5.55). This study suggests that tEPEC contributes to morbidity and mortality in children. Interventions aimed at defining and reducing the burden of tEPEC and its sequelae should be urgently investigated, prioritised and implemented.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
The radiocarbon (14C) calibration curve so far contains annually resolved data only for a short period of time. With accelerator mass spectrometry (AMS) matching the precision of decay counting, it is now possible to efficiently produce large datasets of annual resolution for calibration purposes using small amounts of wood. The radiocarbon intercomparison on single-year tree-ring samples presented here is the first to investigate specifically possible offsets between AMS laboratories at high precision. The results show that AMS laboratories are capable of measuring samples of Holocene age with an accuracy and precision that is comparable or even goes beyond what is possible with decay counting, even though they require a thousand times less wood. It also shows that not all AMS laboratories always produce results that are consistent with their stated uncertainties. The long-term benefits of studies of this kind are more accurate radiocarbon measurements with, in the future, better quantified uncertainties.
Introduction: For rhythm control of acute atrial flutter (AAFL) in the emergency department (ED), choices include initial drug therapy or initial electrical cardioversion (ECV). We compared the strategies of pharmacological cardioversion followed by ECV if necessary (Drug-Shock), and ECV alone (Shock Only). Methods: We conducted a randomized, blinded, placebo-controlled trial (1:1 allocation) comparing two rhythm control strategies at 11 academic EDs. We included stable adult patients with AAFL, where onset of symptoms was <48 hours. Patients underwent central web-based randomization stratified by site. The Drug-Shock group received an infusion of procainamide (15mg/kg over 30 minutes) followed 30 minutes later, if necessary, by ECV at 200 joules x 3 shocks. The Shock Only group received an infusion of saline followed, if necessary, by ECV x 3 shocks. The primary outcome was conversion to sinus rhythm for ≥30 minutes at any time following onset of infusion. Patients were followed for 14 days. The primary outcome was evaluated on an intention-to-treat basis. Statistical significance was assessed using chi-squared tests and multivariable logistic regression. Results: We randomized 76 patients, and none was lost to follow-up. The Drug-Shock (N = 33) and Shock Only (N = 43) groups were similar for all characteristics including mean age (66.3 vs 63.4 yrs), duration of AAFL (30.1 vs 24.5 hrs), previous AAFL (72.7% vs 69.8%), median CHADS2 score (1 vs 1), and mean initial heart rate (128.9 vs 126.0 bpm). The Drug-Shock and Shock only groups were similar for the primary outcome of conversion (100% vs 93%; absolute difference 7.0%, 95% CI -0.6;14.6; P = 0.25). The multivariable analyses confirmed the similarity of the two strategies (P = 0.19). In the Drug-Shock group 21.2% of patients converted with the infusion. There were no statistically significant differences for time to conversion (84.2 vs 97.6 minutes), total ED length of stay (9.4 vs 7.5 hours), disposition home (100% vs 95.3%), and stroke within 14 days (0 vs 0). Premature discontinuation of infusion (usually for transient hypotension) was more common in the Drug-Shock group (9.1% vs 0.0%) but there were no serious adverse events. Conclusion: Both the Drug-Shock and Shock Only strategies were highly effective and safe in allowing AAFL patients to go home in sinus rhythm. IV procainamide alone was effective in only one fifth of patients, much less than for acute AF.
Introduction: CAEP recently developed the acute atrial fibrillation (AF) and flutter (AFL) [AAFF] Best Practices Checklist to promote optimal care and guidance on cardioversion and rapid discharge of patients with AAFF. We sought to assess the impact of implementing the Checklist into large Canadian EDs. Methods: We conducted a pragmatic stepped-wedge cluster randomized trial in 11 large Canadian ED sites in five provinces, over 14 months. All hospitals started in the control period (usual care), and then crossed over to the intervention period in random sequence, one hospital per month. We enrolled consecutive, stable patients presenting with AAFF, where symptoms required ED management. Our intervention was informed by qualitative stakeholder interviews to identify perceived barriers and enablers for rapid discharge of AAFF patients. The many interventions included local champions, presentation of the Checklist to physicians in group sessions, an online training module, a smartphone app, and targeted audit and feedback. The primary outcome was length of stay in ED in minutes from time of arrival to time of disposition, and this was analyzed at the individual patient-level using linear mixed effects regression accounting for the stepped-wedge design. We estimated a sample size of 800 patients. Results: We enrolled 844 patients with none lost to follow-up. Those in the control (N = 316) and intervention periods (N = 528) were similar for all characteristics including mean age (61.2 vs 64.2 yrs), duration of AAFF (8.1 vs 7.7 hrs), AF (88.6% vs 82.9%), AFL (11.4% vs 17.1%), and mean initial heart rate (119.6 vs 119.9 bpm). Median lengths of stay for the control and intervention periods respectively were 413.0 vs. 354.0 minutes (P < 0.001). Comparing control to intervention, there was an increase in: use of antiarrhythmic drugs (37.4% vs 47.4%; P < 0.01), electrical cardioversion (45.1% vs 56.8%; P < 0.01), and discharge in sinus rhythm (75.3% vs. 86.7%; P < 0.001). There was a decrease in ED consultations to cardiology and medicine (49.7% vs 41.1%; P < 0.01), but a small but insignificant increase in anticoagulant prescriptions (39.6% vs 46.5%; P = 0.21). Conclusion: This multicenter implementation of the CAEP Best Practices Checklist led to a significant decrease in ED length of stay along with more ED cardioversions, fewer ED consultations, and more discharges in sinus rhythm. Widespread and rigorous adoption of the CAEP Checklist should lead to improved care of AAFF patients in all Canadian EDs.
Introduction: Acute heart failure (AHF) is a common emergency department (ED) presentation and may be associated with poor outcomes. Conversely, many patients rapidly improve with ED treatment and may not need hospital admission. Because there is little evidence to guide disposition decisions by ED and admitting physicians, we sought to create a risk score for predicting short-term serious outcomes (SSO) in patients with AHF. Methods: We conducted prospective cohort studies at 9 tertiary care hospital EDs from 2007 to 2019, and enrolled adult patients who required treatment for AHF. Each patient was assessed for standardized real-time clinical and laboratory variables, as well as for SSO (defined as death within 30 days or intubation, non-invasive ventilation (NIV), myocardial infarction, coronary bypass surgery, or new hemodialysis after admission). The fully pre-specified, logistic regression model with 13 predictors (age, pCO2, and SaO2 were modeled using spline functions with 3 knots and heart rate and creatinine with 5 knots) was fitted to the 10 multiple imputation datasets. Harrell's fast stepdown procedure reduced the number of variables. We calculated the potential impact on sensitivity (95% CI) for SSO and hospital admissions and estimated a sample size of 170 SSOs. Results: The 2,246 patients had mean age 77.4 years, male sex 54.5%, EMS arrival 41.1%, IV NTG 3.1%, ED NIV 5.2%, admission on initial visit 48.6%. Overall there were 174 (7.8%) SSOs including 70 deaths (3.1%). The final risk scale is comprised of five variables (points) and had c-statistic of 0.76 (95% CI: 0.73-0.80): 1.Valvular heart disease (1) 2.ED non-invasive ventilation (2) 3.Creatinine 150-300 (1) ≥300 (2) 4.Troponin 2x-4x URL (1) ≥5x URL (2) 5.Walk test failed (2) The probability of SSO ranged from 2.0% for a total score of 0 to 90.2% for a score of 10, showing good calibration. The model was stable over 1,000 bootstrap samples. Choosing a risk model total point admission threshold of >2 would yield a sensitivity of 80.5% (95% CI 73.9-86.1) for SSO with no change in admissions from current practice (48.6% vs 48.7%). Conclusion: Using a large prospectively collected dataset, we created a concise and sensitive risk scale to assist with admission decisions for patients with AHF in the ED. Implementation of this risk scoring scale should lead to safer and more efficient disposition decisions, with more high-risk patients being admitted and more low-risk patients being discharged.
Introduction: An important challenge physicians face when treating acute heart failure (AHF) patients in the emergency department (ED) is deciding whether to admit or discharge, with or without early follow-up. The overall goal of our project was to improve care for AHF patients seen in the ED while avoiding unnecessary hospital admissions. The specific goal was to introduce hospital rapid referral clinics to ensure AHF patients were seen within 7 days of ED discharge. Methods: This prospective before-after study was conducted at two campuses of a large tertiary care hospital, including the EDs and specialty outpatient clinics. We enrolled AHF patients ≥50 years who presented to the ED with shortness of breath (<7 days). The 12-month before (control) period was separated from the 12-month after (intervention) period by a 3-month implementation period. Implementation included creation of rapid access AHF clinics staffed by cardiology and internal medicine, and development of referral procedures. There was extensive in-servicing of all ED staff. The primary outcome measure was hospital admission at the index visit or within 30 days. Secondary outcomes included mortality and actual access to rapid follow-up. We used segmented autoregression analysis of the monthly proportions to determine whether there was a change in admissions coinciding with the introduction of the intervention and estimated a sample size of 700 patients. Results: The patients in the before period (N = 355) and the after period (N = 374) were similar for age (77.8 vs. 78.1 years), arrival by ambulance (48.7% vs 51.1%), comorbidities, current medications, and need for non-invasive ventilation (10.4% vs. 6.7%). Comparing the before to the after periods, we observed a decrease in hospital admissions on index visit (from 57.7% to 42.0%; P <0.01), as well as all admissions within 30 days (from 65.1% to 53.5% (P < 0.01). The autoregression analysis, however, demonstrated a pre-existing trend to fewer admissions and could not attribute this to the intervention (P = 0.91). Attendance at a specialty clinic, amongst those discharged increased from 17.8% to 42.1% (P < 0.01) and the median days to clinic decreased from 13 to 6 days (P < 0.01). 30-day mortality did not change (4.5% vs. 4.0%; P = 0.76). Conclusion: Implementation of rapid-access dedicated AHF clinics led to considerably increased access to specialist care, much reduced follow-up times, and possible reduction in hospital admissions. Widespread use of this approach can improve AHF care in Canada.
Assess the sources of patients' knowledge of medication side effects and the effects of their knowledge on compliance with prescribed medication.
476 patients attending psychiatric services were randomly selected and asked to fill a questionnaire designed to assess parameters relevant to the objectives of the study.
Overall, 44% said they had learnt of side effects of their medication from multiple sources including doctors (52.31%), leaflets (54.2%), internet (14.29%), books (13.02%), chemist (11.34%), other patients (5.67%), friends/relatives (7.35%), self-help groups (2.94%) and other sources (4.2%). 8% said they were not aware of any side effects of the medicines they are taking presently.
13.44% of patients reported that they never find out about side effects of their medication before taking it for the first time with a high proportion of these being males (17.93%vs.10.69%, p = 0.0366). 46.2% reported that they have had concerns about taking medication because of their knowledge of side effects with females more likely to have such concerns than males (49.83% vs.40.76%, p = 0.0269). Finally, when asked if they would have taken the medicines prescribed for them now if they were told initially of all the side effects, 51.05% answered ‘more likely’, with a higher proportion of these being males (56.67% vs. 49.46%, p = 0.06)
Doctors and information leaflets are the leading sources of patients' knowledge about side effects of medication. The knowledge of side effects of medication has a potential to impact more on the compliance of female patients compared to males.
Subjective reports of dysphoric responses to neuroleptic medication are common in clinical practice. However, cognitive and affective side effects of neuroleptic medications are difficult to differentiate from the symptoms of schizophrenia. We sought to elucidate the relative contribution of extrapyramidal side effects and symptomatology to dysphoric response.
Fifty clinically stable outpatients with schizophrenia attending a rehabilitation centre were assessed for extrapyramidal side effects and symptomatology before completing the drug attitude inventory (DAI).
Presence of extrapyramidal side effects, found in 28 patients (Z = −1.99, p = 0.05), and severity of negative symptoms (r = −0.47, p = 0.001) were independently associated with dysphoric response, explaining a significant proportion of the variance (R = 0.53, R2 = 25.2%, F = 9.27, df = 2, p = 0.0004).
Patients who report a dysphoric response which they associate with neuroleptic medications have more extrapyramidal side effects and more severe negative symptoms. While these responses may be part of the negative symptoms of the illness or due to other factors such as depression, we raise the possibility that they may be clinically indistinguishable from, and be a subjective measure of, the so-called ‘neuroleptic-induced deficit syndrome’.
Commonly used measures of instrumental activities of daily living (IADL) do not capture activities for a technologically advancing society. This study aimed to adapt the proxy/informant-based Amsterdam IADL Questionnaire (A-IADL-Q) for use in the UK and develop a self-report version.
An iterative mixed method cross-cultural adaptation of the A-IADL-Q and the development of a self-report version involving a three-step design: (1) interviews and focus groups with lay and professional stakeholders to assess face and content validity; (2) a questionnaire to measure item relevance to older adults in the U.K.; (3) a pilot of the adapted questionnaire in people with cognitive impairment.
Community settings in the UK.
One hundred and forty-eight participants took part across the three steps: (1) 14 dementia professionals; 8 people with subjective cognitive decline (SCD), mild cognitive impairment (MCI), or dementia due to Alzheimer’s disease; and 6 relatives of people with MCI or dementia; (2) 92 older adults without cognitive impairment; and (3) 28 people with SCD or MCI.
The cultural relevance and applicability of the A-IADL-Q scale items were assessed using a 6-point Likert scale. Cognitive and functional performance was measured using a battery of cognitive and functional measures.
Iterative modifications to the scale resulted in a 55-item adapted version appropriate for UK use (A-IADL-Q-UK). Pilot data revealed that the new and revised items performed well. Four new items correlated with the weighted average score (Kendall’s Tau −.388, −.445, −.497, −.569). An exploratory analysis of convergent validity found correlations in the expected direction with cognitive and functional measures.
The A-IADL-Q-UK provides a measurement of functional decline for use in the UK that captures culturally relevant activities. A new self-report version has been developed and is ready for testing. Further evaluation of the A-IADL-Q-UK for construct validity is now needed.
Participation in European surveillance for bloodstream infection (BSI) commenced in Ireland in 1999 with all laboratories (n = 39) participating by 2014. Observational hand hygiene auditing (OHHA) was implemented in 2011. The aim of this study was to evaluate the impact of OHHA on hand hygiene compliance, alcohol hand rub (AHR) procurement and the incidence of sensitive and resistant Staphylococcus aureus and Enterococcus faecium and faecalis BSI. A prospective segmented regression analysis was performed to determine the temporal association between OHHA and outcomes. Observed hand hygiene improved from 74.7% (73.7–75.6) in 2011 to 90.8% (90.1–91.3) in 2016. AHR procurement increased from 20.1 l/1000 bed days used (BDU) in 2009 to 33.2 l/1000 BDU in 2016. A pre-intervention reduction of 2% per quarter in the ratio of methicillin sensitive Staphylococcus aureus BSI/BDU stabilized in the time period after the intervention (P < 0.01). The ratio of Methicillin resistant Staphylococcus aureus (MRSA) BSI/BDU was decreasing by 5% per quarter pre-intervention, this slowed to 2% per quarter post intervention, (P < 0.01). There was no significant change in the ratio of vancomycin sensitive (P = 0.49) or vancomycin resistant (P = 0.90) Enterococcus sp. BSI/BDU post intervention. This study shows national OHHA increased observed hand hygiene compliance and AHR procurement, however there was no associated reduction in BSI.
The Genomics Used to Improve DEpresssion Decisions (GUIDED) trial assessed outcomes associated with combinatorial pharmacogenomic (PGx) testing in patients with major depressive disorder (MDD). Analyses used the 17-item Hamilton Depression (HAM-D17) rating scale; however, studies demonstrate that the abbreviated, core depression symptom-focused, HAM-D6 rating scale may have greater sensitivity toward detecting differences between treatment and placebo. However, the sensitivity of HAM-D6 has not been tested for two active treatment arms. Here, we evaluated the sensitivity of the HAM-D6 scale, relative to the HAM-D17 scale, when assessing outcomes for actively treated patients in the GUIDED trial.
Outpatients (N=1,298) diagnosed with MDD and an inadequate treatment response to >1 psychotropic medication were randomized into treatment as usual (TAU) or combinatorial PGx-guided (guided-care) arms. Combinatorial PGx testing was performed on all patients, though test reports were only available to the guided-care arm. All patients and raters were blinded to study arm until after week 8. Medications on the combinatorial PGx test report were categorized based on the level of predicted gene-drug interactions: ‘use as directed’, ‘moderate gene-drug interactions’, or ‘significant gene-drug interactions.’ Patient outcomes were assessed by arm at week 8 using HAM-D6 and HAM-D17 rating scales, including symptom improvement (percent change in scale), response (≥50% decrease in scale), and remission (HAM-D6 ≤4 and HAM-D17 ≤7).
At week 8, the guided-care arm demonstrated statistically significant symptom improvement over TAU using HAM-D6 scale (Δ=4.4%, p=0.023), but not using the HAM-D17 scale (Δ=3.2%, p=0.069). The response rate increased significantly for guided-care compared with TAU using both HAM-D6 (Δ=7.0%, p=0.004) and HAM-D17 (Δ=6.3%, p=0.007). Remission rates were also significantly greater for guided-care versus TAU using both scales (HAM-D6 Δ=4.6%, p=0.031; HAM-D17 Δ=5.5%, p=0.005). Patients taking medication(s) predicted to have gene-drug interactions at baseline showed further increased benefit over TAU at week 8 using HAM-D6 for symptom improvement (Δ=7.3%, p=0.004) response (Δ=10.0%, p=0.001) and remission (Δ=7.9%, p=0.005). Comparatively, the magnitude of the differences in outcomes between arms at week 8 was lower using HAM-D17 (symptom improvement Δ=5.0%, p=0.029; response Δ=8.0%, p=0.008; remission Δ=7.5%, p=0.003).
Combinatorial PGx-guided care achieved significantly better patient outcomes compared with TAU when assessed using the HAM-D6 scale. These findings suggest that the HAM-D6 scale is better suited than is the HAM-D17 for evaluating change in randomized, controlled trials comparing active treatment arms.
− Agency is one of five core analytical problems in the Earth System Governance (ESG) Project’s research framework, which offers a unique approach to the study of environmental governance. − Agency in Earth System Governance draws lessons from ESG–Agency research through a systematic review of 322 peer-reviewed journal articles published between 2008 and 2016 and contained in the ESG–Agency Harvesting Database.− ESG–Agency research draws on diverse disciplinary perspectives with distinct clusters of scholars rooted in the fields of global environmental politics, policy studies, and socio-ecological systems. − Collectively, the chapters in Agency in Earth System Governance provide an accessible synthesis of some of the field’s major questions and debates and a state-of-the-art understanding of how diverse actors engage with and exercise authority in environmental governance.
5-HT4 receptor stimulation has pro-cognitive and antidepressant-like effects in animal experimental studies; however, this pharmacological approach has not yet been tested in humans. Here we used the 5-HT4 receptor partial agonist prucalopride to assess the translatability of these effects and characterise, for the first time, the consequences of 5-HT4 receptor activation on human cognition and emotion.
Forty one healthy volunteers were randomised, double-blind, to a single dose of prucalopride (1 mg) or placebo in a parallel group design. They completed a battery of cognitive tests measuring learning and memory, emotional processing and reward sensitivity.
Prucalopride increased recall of words in a verbal learning task, increased the accuracy of recall and recognition of words in an incidental emotional memory task and increased the probability of choosing a symbol associated with a high likelihood of reward or absence of loss in a probabilistic instrumental learning task. Thus acute prucalopride produced pro-cognitive effects in healthy volunteers across three separate tasks.
These findings are a translation of the memory enhancing effects of 5-HT4 receptor agonism seen in animal studies, and lend weight to the idea that the 5-HT4 receptor could be an innovative target for the treatment of cognitive deficits associated with depression and other neuropsychiatric disorders. Contrary to the effects reported in animal models, prucalopride did not reveal an antidepressant profile in human measures of emotional processing.